Session: MON 338-354-Physiological Impacts of Endocrine Disrupting Chemicals
Poster Board MON-345
We investigated how BPA treatment on female rat myocytes affected two key cardiac Ca2+ handling proteins: Ryanodine receptor (RyR) and phospholamban (PLN). RyR mediates Ca2+ release from SR while PLN regulates SR Ca2+ reuptake process, and both proteins could be phosphorylated by Kinases to increase their activities and alter Ca2+ cycling. Using western blots we found that under BPA treatment, RyR phosphorylation increased within 5 minutes at PKA’s site (RyR2808), but not CAMKII’s site (RyR2814); while PLN phosphorylation increased with similar time course at CAMKII’s site (PLN17), but not PKA’s site (PLN16). The increases of phosphorylation on both RyR and PLN are diminished with the treatment of ERb blocker, but not ERa blocker. When blockers for PKA or CAMKII were applied together with BPA, the effect of BPA on RyR and PLN phosphorylation were completely abolished. We performed Ca2+ sparks study to examine the SR Ca2+ release from RyR, and we observed that PKA blockers completely blunted Ca2+ spark increase induced by BPA. Then we measured the “triggered activities” on myocytes through both after-contraction and after-transient experiments, which are direct indicators for the arrhythmogenesis on the myocyte. We found that both PKA and CAMKII blockers completely abolished the “triggered activities” induced by BPA, which pointed to the important roles of these two kinases in the arrhythmogenic effects of BPA in the female heart.
In conclusion, our results demonstrate that BPA promotes cardiac arrhythmias via activation of PKA and CAMKII signaling pathways, and altering the phosphorylation of key cardiac Ca2+ handling proteins.
Nothing to Disclose: XG, QL, YC, HSW
*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm
See more of: Abstracts - Orals, Featured Poster Presentations, and Posters